The usefulness of an animal model for the study of anti-caries immunity is dependent upon several well defined parameters. These include the pathogenicity of the test bacterium, suceptibility of the host animal to caries attack by this microorganism, the specificity of caries attack and the immune response to this bacterium including immunoglobulin levels and specific antibodies. Gnotobiotic rats maintained in Trexlar flexible isolators, fed a defined diet containing 5% sucrose and infected with a hyper-cariogenic mutant of streptococcus mutans has provided such a model for our studies. Using this model we have investigated effective methods for induction of caries immunity and characterization of the immune mechanisms involved. In early studies in the laboratory, it was found that local injection in the region of the salivary glands resulted in a significant secretory immune response which afforded protection against subsequent caries attack. Later studies indicated that similar protective responses could be induced by ingestion of killed S. mutans in the drinking water or food. This response was probably due to stimulation of precursor secretory IgA lymphocytes in the gut associated lymphoid tissue which subsequently seed to the remote secretory tissues such as mammary and salivary glands. This hypothesis is supported by the fact that introduction of the antigen by gastric intubation (by-passing the oral cavity) results in an equivalent response. Current studies are being directed at optimizing the dosage and schedule of administration of antigen, and characterization of protective antigenic determinants. The cellular aspects of this response including homing and subsequent antibody formation are also being investigated. The dynamics of the secretory immune response are being considered including the potential for an anamnestic response. The role of non-specific immune factors, lactoferrin, lysozyme and lactoperoxidase in caries immunity are being studied in vivo and in vitro. Purified lactoferrin has been found to be bactericidal for S. mutans and certain other microorganims at physiological concentrations. Other in vitro studies are looking at possible interactions between purified s-IgA antibodies, lactoferrin, lysozyme and lactoperoxidase.